Suppression of 6A8 α‐mannosidase gene expression reduced the potentiality of growth and metastasis of human nasopharyngeal carcinoma

Abstract

Suppression of ␣-mannosidases by chemicals has been shown to reduce the potentiality of growth and metastasis of various tumors. In our study, the effect of 6A8 ␣-mannosidase (MAN 6A8), recently discovered in our laboratory, on malignant behaviors of tumor cells was examined. Since the suppressive effect of chemicals on ␣-mannosidase is not specific, antisense technique was used to specifically inhibit expression of the MAN 6A8 in human nasopharyngeal carcinoma cells, CNE-2L2. Key words: ␣-mannosidase; tumor; growth; metastasis; antisense; E-cadherinInhibition of ␣-mannosidase has been found to show suppressive effect on malignant behaviors of tumor cells. [1][2][3] In examining the effect of ␣-mannosidase on growth and metastasis of tumors, chemicals, such as swainsonine, 1-deoxymannojirimycin, mannostatin, etc., have been normally used to inhibit ␣-mannosidase. 1,3-5 Among the chemicals, swainsonine is the one rather widely used that has been tested even in preliminary clinical trials in late-stage cancer patients and was shown to induce partial remission of tumor in 1 and symptomatic improvement in 2 of 19 patients. 6,7 Recently, we isolated a cDNA encoding a novel human ␣-mannosidase (MAN 6A8). 8 In searching the EST database of the Cancer Genome Anatomy Project for 6A8 gene expression in various tissues, we found an enhancement of 6A8 gene expression in a number of cancer tissues, including bone, bone marrow, brain, esophagus, eye, genitourinary, germ cell, nervous, pineal gland, soft tissue cancers, etc., suggesting a possible role of MAN 6A8 in tumorigenesis. Hence, the relationship between MAN 6A8 gene expression and malignant behaviors of tumor cells has been critically examined. Our study was carried out on a human nasopharyngeal carcinoma cell line, CNE-2L2. Because the chemicals mentioned above cannot specifically suppress a given ␣-mannosidase and usually have side effects 1 and particularly because swainsonine has no effect on MAN 6A8, 8 we used the antisense technique 9 to inhibit mRNA translation of MAN 6A8. It was found that the malignant behaviors of CNE-2L2 cells, both in vitro and in vivo, were significantly reduced when MAN 6A8 expression was inhibited. Since morphologic observation showed that cultured CNE-2L2 cells with inhibited MAN 6A8 expression became compact sheets instead of being dispersed as compared to the controls and since cell-cell adhesion of epithelial cells is mainly mediated by E-cadherin 10 and loss of E-cadherin expression plays an important role in the growth and metastasis of tumors, 11-16 expression of E-cadherin was assayed in CNE-2L2 cells. An enhancement of E-cadherin expression was found in cells with inhibited MAN 6A8 expression.The results demonstrate a significant inhibitive effect of reduced expression of MAN6A8 on the malignant behaviors of CNE-2L2 cells and suggest the possibility of the enzyme being a target molecule in the treatment of nasopharyngeal carcinoma. MATERIAL AND METHODS Cell line and animalCNE-2L2 is a cloned cell line isolated from CNE-2Z, a h...

Dual Functions for Cytosolic α-Mannosidase (Man2C1)

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Accumulation of Free Oligosaccharides and Tissue Damage in Cytosolic α-Mannosidase (Man2c1)-deficient Mice

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Downregulation of PLK1 by RNAi attenuates the tumorigenicity of esophageal squamous cell carcinoma cells via promoting apoptosis and inhibiting angiogenesis

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